It is difficult to sterilize biological cell compositions for prophylactic and therapeutic purposes because the chemical, physical, or physiological properties of the cells can be significantly altered by variations in the cells' surrounding environment. For example, gas sterilization using, for example, ethylene oxide, is known to be toxic and also carcinogenic. Irradiation with about 1-3 mRads (megarads), while sufficient to kill microorganisms, can alter the structure of proteins, DNA, RNA, etc. and either biologically modify the cells or render the cells totally inactive for their intended immunogenic or other biological function. These difficulties are exasperated when it is important that any chemical or physical means employed achieve not only a high level of sterility but also substantially no reduction in the metabolic and immunogenic properties of the cells.
U.S. Pat. No. 5,484,596 (“the '596 patent”) entitled “Active Specific Immunotherapy” relates to a method for treating human colon cancer patients with resectable solid tumors to inhibit recurrence and formation of metastases. The method comprises surgically removing colon tumor tissue from a human cancer patient, treating the tumor tissue to obtain tumor cells, irradiating the tumor cells (with 20,000 rads) to be viable but non-tumorigenic, preparing a vaccine comprising viable but non-tumorigenic tumor cells, and injecting the vaccine intradermally after the cancer patient's immune system has recovered from surgery.
By virtue of the origin of colon tumors within the large bowel, cancer vaccines produced by the process of the '596 patent are not sterile. Although the vaccine product (OncoVAX®) prepared according to that patent has already been administered to several hundred human patients, regulatory authorities now require that such vaccine products must be sterile. To obtain an immunogenic cell preparation, the tumor cells must be viable and metabolically active. Thus any treatment to render the cells sterile must not unduly compromise the essential biological characteristics of the cells required for efficacy. What is needed is a process that renders cell preparations sterile, while maintaining viability and immunogenicity. Preferably, such a sterilization process can be easily integrated into existing product manufacturing processes.
The present invention is directed to achieving safe, sterile tumor cell compositions, without incurring substantial changes to the immunogenic properties of the tumor cells. These goals are not necessarily compatible. For example, sterilization can inactivate microbial infection but also can substantially inactivate mammalian cells; disinfectants kill microbes but can also kill mammalian cells; and radiation can render microbial infection inactive but can also substantially modify the immunogenic and other properties of mammalian cells. It is therefore desirable to provide a process for obtaining sterile non-tumorigenic tumor cell compositions which does not substantially interfere with essential metabolic and immunogenic properties of the cells.